pH-Responsive Triblock Copolymeric Micelles Decorated with a Cell-Penetrating Peptide Provide Efficient Doxorubicin Delivery

Khen Eng Ng, Mohd Cairul Iqbal Mohd Amin, Haliza Katas, Muhammad Wahab Amjad, Adeel Masood Butt, Prashant Kesharwani, Arun K. Iyer

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Abstract: This study developed novel triblock pH-responsive polymeric micelles (PMs) using cholic acid-polyethyleneimine-poly-l-arginine (CA-PEI-pArg) copolymers. PEI provided pH sensitivity, while the hydrophilic cell-penetrating pArg peptide promoted cellular PM internalization. The copolymers self-assembled into PMs in aqueous solution at above the critical micelle concentration (2.98 × 10−7 M) and encapsulated doxorubicin in the core region, with a 34.2% (w/w) entrapment efficiency. PMs showed pH-dependent swelling, increasing in size by almost sevenfold from pH 7.4 to 5.0. Doxorubicin release was pH-dependent, with about 65% released at pH 5.0, and 32% at pH 7.4. Cellular uptake, assessed by confocal microscopy and flow cytometry, was enhanced by using doxorubicin-loaded CA-PEI-pArg PMs, as compared to free doxorubicin and DOX-loaded CA-PEI PMs. Moreover, 24-h incubation of these PMs with a human breast cancer cell line produced greater cytotoxicity than free doxorubicin. These results indicate that pH-responsive CA-PEI-pArg micelles could provide a versatile delivery system for targeted cancer therapy using hydrophobic drugs. Graphical Abstract: Graphical of CA-PEI-pArg polymeric micelles as a pH-responsive drug delivery system.

Original languageEnglish
Article number539
JournalNanoscale Research Letters
Volume11
Issue number1
DOIs
Publication statusPublished - 1 Dec 2016

Fingerprint

Cell-Penetrating Peptides
Micelles
Doxorubicin
Peptides
peptides
delivery
micelles
Cholic Acid
Polyethyleneimine
Arginine
cells
Polyetherimides
Acids
acids
Copolymers
copolymers
drugs
cancer
Flow cytometry
Critical micelle concentration

Keywords

  • Doxorubicin
  • Drug delivery
  • pH responsive
  • Polyarginine
  • Polymeric micelle
  • Triblock copolymer

ASJC Scopus subject areas

  • Materials Science(all)
  • Condensed Matter Physics

Cite this

pH-Responsive Triblock Copolymeric Micelles Decorated with a Cell-Penetrating Peptide Provide Efficient Doxorubicin Delivery. / Ng, Khen Eng; Mohd Amin, Mohd Cairul Iqbal; Katas, Haliza; Amjad, Muhammad Wahab; Butt, Adeel Masood; Kesharwani, Prashant; Iyer, Arun K.

In: Nanoscale Research Letters, Vol. 11, No. 1, 539, 01.12.2016.

Research output: Contribution to journalArticle

@article{c75254b6ca8b47d09142b1a4fa8065e8,
title = "pH-Responsive Triblock Copolymeric Micelles Decorated with a Cell-Penetrating Peptide Provide Efficient Doxorubicin Delivery",
abstract = "Abstract: This study developed novel triblock pH-responsive polymeric micelles (PMs) using cholic acid-polyethyleneimine-poly-l-arginine (CA-PEI-pArg) copolymers. PEI provided pH sensitivity, while the hydrophilic cell-penetrating pArg peptide promoted cellular PM internalization. The copolymers self-assembled into PMs in aqueous solution at above the critical micelle concentration (2.98 × 10−7 M) and encapsulated doxorubicin in the core region, with a 34.2{\%} (w/w) entrapment efficiency. PMs showed pH-dependent swelling, increasing in size by almost sevenfold from pH 7.4 to 5.0. Doxorubicin release was pH-dependent, with about 65{\%} released at pH 5.0, and 32{\%} at pH 7.4. Cellular uptake, assessed by confocal microscopy and flow cytometry, was enhanced by using doxorubicin-loaded CA-PEI-pArg PMs, as compared to free doxorubicin and DOX-loaded CA-PEI PMs. Moreover, 24-h incubation of these PMs with a human breast cancer cell line produced greater cytotoxicity than free doxorubicin. These results indicate that pH-responsive CA-PEI-pArg micelles could provide a versatile delivery system for targeted cancer therapy using hydrophobic drugs. Graphical Abstract: Graphical of CA-PEI-pArg polymeric micelles as a pH-responsive drug delivery system.",
keywords = "Doxorubicin, Drug delivery, pH responsive, Polyarginine, Polymeric micelle, Triblock copolymer",
author = "Ng, {Khen Eng} and {Mohd Amin}, {Mohd Cairul Iqbal} and Haliza Katas and Amjad, {Muhammad Wahab} and Butt, {Adeel Masood} and Prashant Kesharwani and Iyer, {Arun K.}",
year = "2016",
month = "12",
day = "1",
doi = "10.1186/s11671-016-1755-4",
language = "English",
volume = "11",
journal = "Nanoscale Research Letters",
issn = "1931-7573",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - pH-Responsive Triblock Copolymeric Micelles Decorated with a Cell-Penetrating Peptide Provide Efficient Doxorubicin Delivery

AU - Ng, Khen Eng

AU - Mohd Amin, Mohd Cairul Iqbal

AU - Katas, Haliza

AU - Amjad, Muhammad Wahab

AU - Butt, Adeel Masood

AU - Kesharwani, Prashant

AU - Iyer, Arun K.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Abstract: This study developed novel triblock pH-responsive polymeric micelles (PMs) using cholic acid-polyethyleneimine-poly-l-arginine (CA-PEI-pArg) copolymers. PEI provided pH sensitivity, while the hydrophilic cell-penetrating pArg peptide promoted cellular PM internalization. The copolymers self-assembled into PMs in aqueous solution at above the critical micelle concentration (2.98 × 10−7 M) and encapsulated doxorubicin in the core region, with a 34.2% (w/w) entrapment efficiency. PMs showed pH-dependent swelling, increasing in size by almost sevenfold from pH 7.4 to 5.0. Doxorubicin release was pH-dependent, with about 65% released at pH 5.0, and 32% at pH 7.4. Cellular uptake, assessed by confocal microscopy and flow cytometry, was enhanced by using doxorubicin-loaded CA-PEI-pArg PMs, as compared to free doxorubicin and DOX-loaded CA-PEI PMs. Moreover, 24-h incubation of these PMs with a human breast cancer cell line produced greater cytotoxicity than free doxorubicin. These results indicate that pH-responsive CA-PEI-pArg micelles could provide a versatile delivery system for targeted cancer therapy using hydrophobic drugs. Graphical Abstract: Graphical of CA-PEI-pArg polymeric micelles as a pH-responsive drug delivery system.

AB - Abstract: This study developed novel triblock pH-responsive polymeric micelles (PMs) using cholic acid-polyethyleneimine-poly-l-arginine (CA-PEI-pArg) copolymers. PEI provided pH sensitivity, while the hydrophilic cell-penetrating pArg peptide promoted cellular PM internalization. The copolymers self-assembled into PMs in aqueous solution at above the critical micelle concentration (2.98 × 10−7 M) and encapsulated doxorubicin in the core region, with a 34.2% (w/w) entrapment efficiency. PMs showed pH-dependent swelling, increasing in size by almost sevenfold from pH 7.4 to 5.0. Doxorubicin release was pH-dependent, with about 65% released at pH 5.0, and 32% at pH 7.4. Cellular uptake, assessed by confocal microscopy and flow cytometry, was enhanced by using doxorubicin-loaded CA-PEI-pArg PMs, as compared to free doxorubicin and DOX-loaded CA-PEI PMs. Moreover, 24-h incubation of these PMs with a human breast cancer cell line produced greater cytotoxicity than free doxorubicin. These results indicate that pH-responsive CA-PEI-pArg micelles could provide a versatile delivery system for targeted cancer therapy using hydrophobic drugs. Graphical Abstract: Graphical of CA-PEI-pArg polymeric micelles as a pH-responsive drug delivery system.

KW - Doxorubicin

KW - Drug delivery

KW - pH responsive

KW - Polyarginine

KW - Polymeric micelle

KW - Triblock copolymer

UR - http://www.scopus.com/inward/record.url?scp=85001945972&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85001945972&partnerID=8YFLogxK

U2 - 10.1186/s11671-016-1755-4

DO - 10.1186/s11671-016-1755-4

M3 - Article

AN - SCOPUS:85001945972

VL - 11

JO - Nanoscale Research Letters

JF - Nanoscale Research Letters

SN - 1931-7573

IS - 1

M1 - 539

ER -